Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document. Methods ICAR‐Allergic Rhinitis 2023 employed established evidence‐based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR‐Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR‐Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.
Abstract. In the present study we analyzed the anti-proliferative effect of tocilizumab, a humanized recombinant monoclonal interleukin 6 receptor (IL-6R) antibody, against non-small cell lung cancer (NSCLC) cells, including A549, H460, H358 and H1299 cells. The cell cycle distribution of NSCLCs was analyzed using fluorescence-activated cell sorting and gene expression using quantitative polymerase chain reaction. Cell lysates treated with tocilizumab were immunoblotted with antibodies against signal transducer and activator of transcription 3 (STAT3), phospho-STAT3, extracellular-signal-regulated kinases (ERK), phospho-ERK, nuclear factor κB (NFκB) and phospho-NFκB. Significant growth inhibition of NSCLC cells was observed following treatment with tocilizumab. Proliferation was significantly decreased by approximately 10-40% in A549, H460, H1299 and H358 cells, with an inhibition rate that was comparable with that of the typical anticancer drugs methotrexate and 5-fluorouracil. NSCLC cell populations were accumulated in the sub-G1 phase by treatment with tocilizumab. Western blot analyses revealed a possible activation of the NFκB pathway by tocilizumab. Overall, these data indicate that tocilizumab has anticancer potency via apoptosis induction as an agonistic IL-6R regulator. Therefore, we suggest that this anti-IL-6R antibody may be utilized as a new targeting molecule for NSCLC therapies. IntroductionNon-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of cases. As a class, NSCLC is relatively insensitive to chemotherapy compared with small cell carcinoma. A number of drugs are useful for NSCLC as systemic therapy, including platinum agents (cisplatin and carboplatin), taxanes (paclitaxel and docetaxel), vinorelbine, vinblastine, etoposide, pemetrexed and gemcitabine. However, despite advances in chemotherapeutic drugs, the prognosis of lung cancer remains poor, with an overall 5-year survival rate of less than 14% in the USA and even lower (5-10%) in Europe and other countries (1).A number of investigators have attempted to develop specific targeting molecules, including antibodies and antagonists, for the treatment of NSCLC. Bevacizumab is a recombinant monoclonal antibody that blocks vascular endothelial growth factor. Erlotinib is a small molecule inhibitor of epidermal growth factor receptor (EGFR), and crizotinib is a small molecule inhibitor that targets anaplastic lymphoma kinase and hepatocyte growth factor receptor c-MET. Cetuximab is a monoclonal antibody that targets EGFR.The pathway of interleukin 6/interleukin 6 receptor (IL-6/IL-6R) signaling regulates diverse biological activities, including cell growth and differentiation, in immune and hematopoietic systems (2). However, IL-6/IL-6R signaling is also known to promote tumor growth and survival in several organ systems (3). The plasma IL-6 levels of cancer patients were observed to correlate with the clinical and pathological variety and survival in prostate cancer (4), ovarian cancer (5), br...
Abstract. The aim of this study was to develop an analytical method for detection of imidocarb [1,3-bis[3-(4,5-dihydro-1h-imidazol-2-yl)phenyl]urea] in beef and milk using high-performance liquid chromatography (HPLC) with diode-array detection (DAD). Imidocarb was separated on a reversed-phase column (4.6x250 mm, 5 µm) with a mobile phase consisting of 85:15 (v/v) 0.1% trifluoroacetic acid/acetonitrile. The flow rate was 1 ml/min, and the column temperature was maintained at 20˚C. Detection was carried out at 260 nm using a DAD detector. The analytical samples were extracted using a solid-phase extraction (SPE) method. The calibration curves showed good linearity (r≥0.998). Limits of quantifications (LOQs) were 0.15 mg/kg in beef and 0.025 mg/kg in milk. Intra-and inter-day precisions were 3.2-6.1 and 1.4-6.9%, respectively, and the accuracy (recovery) was 80.4-82.2% and 80.1-89.5% in beef and milk, respectively. Thus, an analytical protocol using SPE extraction followed by HPLC with DAD was successfully developed, which demonstrated acceptable precision and recovery.
A quick, easy, cheap, effective, rugged, and safe QuEChERS (method) was used for the simultaneous detection of four veterinary drug residues, namely naloxone, yohimbine, thiophanate, and altrenogest, in porcine muscle, using liquid chromatography with electrospray ionization triple quadrupole tandem mass spectrometry. Because of the unavailability of a suitable internal standard, matrix-matched calibrations were used for quantification, with determination coefficients ≥ 0.9542. The accuracy (expressed as recovery %) ranged from 60.53 to 83.25%, and the intra- and interday precisions (expressed as relative standard deviations) were <12%. The limits of quantification were 5, 0.5, 2, and 5 ng/g for naloxone, yohimbine, thiophanate, and altrenogest, respectively. Samples purchased from local markets in Seoul, Republic of Korea, revealed no traces of the target analytes. The developed method described herein is sensitive and reliable and can be applied to quantify the tested veterinary drugs in animal tissues.
Abstract. The present study investigated the preventive effect of ω-3 fatty acids against cholesterol gallstone (CG) formation. CG formation was induced in C57BL/6J mice using a lithogenic diet (LD). The mice were divided into four treatment groups: i) LD, ii) LD plus eicosapentaenoic acid (EPA), iii) LD plus docosahexaenoic acid (DHA) and iv) LD plus EPA plus DHA. Subsequent to feeding the mice the LD for four weeks, EPA and/or DHA (70 mg/kg/day) were orally administered for eight weeks. The mice in the EPA treatment groups exhibited significantly less gallstone formation than those in the LD group. By contrast, DHA treatment only slightly suppressed gallstone formation. The expression of mucin 2, 5AC, 5B and 6 was significantly decreased in the gallbladders of mice in the EPA groups (70-90%) and the LD plus DHA group (30-50%), compared with that in the mice in the LD group. In addition, the mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase was significantly decreased in the livers of mice in the EPA treatment group compared with that in the livers of mice in the LD group. In conclusion, EPA was found to have a dominant anti-lithogenic effect in C57BL/6J mice. IntroductionEicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential fatty acids belonging to the group of ω-3 fatty acids, which are primarily found in coldwater fish. These polyunsaturated fatty acids (PUFAs) have an important role in the functions of the body and are converted into hormone-like substances known as prostaglandins and leukotrienes (1). EPA has been shown to provide health benefits in patients with coronary heart disease, high blood pressure, mental health conditions, such as schizophrenia, and inflammatory disorders, including rheumatoid arthritis (2-6). DHA is a key component of brain tissue and the retina of the eye (7,8). Low levels of DHA cause reduced serotonin levels in the brain, which may result in depression, attention deficit hyperactivity disorder, cognitive decline and Alzheimer's disease (9-11).It is well established that the key factors associated with cholesterol gallstone (CG) formation are biliary cholesterol hypersaturation and gallbladder mucin hypersecretion. The hypersaturation of cholesterol in the bile may result from a high-cholesterol diet or hepatic cholesterol overproduction. The elevation of biliary cholesterol concentration leads to the hypersecretion of mucin and the aggregation of cholesterol crystals (12,13). Several mucin (MUC) genes, including MUC2, MUC5AC, MUC5B and MUC6, are expressed in the gallbladder mucosa (14). The upregulation of these MUC genes leads to increased mucin concentrations, which increase bile viscosity and lead to the formation of a gel matrix that can entrap cholesterol crystals in the gallbladder (15-16).The only established medical treatment for CG is ursodeoxycholic acid (UDCA). However, a number of studies have demonstrated that the therapeutic efficacy exhibited by UDCA lacks consistency and is not entirely satisfactory (17-19). Despite numerous...
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